Use of Corneal Confocal Microscopy to Detect Corneal Nerve Loss and Increased Dendritic Cells in Patients With Multiple Sclerosis

AbstractAxonal loss is the main determinant of disease progression in multiple sclerosis (MS). This study aimed to assess the utility of corneal confocal microscopy (CCM) in detecting corneal axonal loss in different courses of MS. The results were confirmed by two independent segmentation methods. 72 subjects (144 eyes) [(clinically isolated syndrome (n = 9); relapsing–remitting MS (n = 20); secondary-progressive MS (n = 22); and age-matched, healthy controls (n = 21)] underwent CCM and assessment of their disability status. Two independent algorithms (ACCMetrics; and Voxeleron deepNerve) were used to quantify corneal nerve fiber density (CNFD) (ACCMetrics only), corneal nerve fiber length (CNFL) and corneal nerve fractal dimension (CNFrD). Data are expressed as mean ± standard deviation with 95% confidence interval (CI). Compared to controls, patients with MS had significantly lower CNFD (34.76 ± 5.57 vs. 19.85 ± 6.75 fibers/mm2, 95% CI − 18.24 to − 11.59, P < .0001), CNFL [for ACCMetrics: 19.75 ± 2.39 vs. 12.40 ± 3.30 mm/mm2, 95% CI − 8.94 to − 5.77, P < .0001; for deepNerve: 21.98 ± 2.76 vs. 14.40 ± 4.17 mm/mm2, 95% CI − 9.55 to − 5.6, P < .0001] and CNFrD [for ACCMetrics: 1.52 ± 0.02 vs. 1.45 ± 0.04, 95% CI − 0.09 to − 0.05, P < .0001; for deepNerve: 1.29 ± 0.03 vs. 1.19 ± 0.07, 95% − 0.13 to − 0.07, P < .0001]. Corneal nerve parameters were comparably reduced in different courses of MS. There was excellent reproducibility between the algorithms. Significant corneal axonal loss is detected in different courses of MS including patients with clinically isolated syndrome.

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Corneal dendritic cells and the subbasal nerve plexus following neurotoxic treatment with oxaliplatin or paclitaxel

Scientific Reports ◽

10.1038/s41598-021-02439-0 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Jeremy Chung Bo Chiang ◽

David Goldstein ◽

Azadeh Tavakoli ◽

Terry Trinh ◽

Jacob Klisser ◽

...

Keyword(s):

Dendritic Cells ◽

Dendritic Cell ◽

Confocal Microscopy ◽

Immune Cell ◽

Healthy Controls ◽

Corneal Confocal Microscopy ◽

Significant Difference ◽

Corneal Nerve ◽

Cell Densities

AbstractImmune cell infiltration has been implicated in neurotoxic chemotherapy for cancer treatment. However, our understanding of immune processes is still incomplete and current methods of observing immune cells are time consuming or invasive. Corneal dendritic cells are potent antigen-presenting cells and can be imaged with in-vivo corneal confocal microscopy. Corneal dendritic cell densities and nerve parameters in patients treated with neurotoxic chemotherapy were investigated. Patients treated for cancer with oxaliplatin (n = 39) or paclitaxel (n = 48), 3 to 24 months prior to assessment were recruited along with 40 healthy controls. Immature (ImDC), mature (MDC) and total dendritic cell densities (TotalDC), and corneal nerve parameters were analyzed from in-vivo corneal confocal microscopy images. ImDC was increased in the oxaliplatin group (Median, Md = 22.7 cells/mm2) compared to healthy controls (Md = 10.1 cells/mm2, p = 0.001), but not in the paclitaxel group (Md = 10.6 cells/mm2). ImDC was also associated with higher oxaliplatin cumulative dose (r = 0.33, p = 0.04) and treatment cycles (r = 0.40, p = 0.01). There was no significant difference in MDC between the three groups (p > 0.05). Corneal nerve parameters were reduced in both oxaliplatin and paclitaxel groups compared to healthy controls (p < 0.05). There is evidence of elevation of corneal ImDC in oxaliplatin-treated patients. Further investigation is required to explore this potential link through longitudinal studies and animal or laboratory-based immunohistochemical research.

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Corneal confocal microscopy detects corneal nerve damage and increased dendritic cells in Fabry disease

Scientific Reports ◽

10.1038/s41598-018-30688-z ◽

2018 ◽

Vol 8 (1) ◽

Cited By ~ 10

Author(s):

Gulfidan Bitirgen ◽

Kultigin Turkmen ◽

Rayaz A. Malik ◽

Ahmet Ozkagnici ◽

Nazmi Zengin

Keyword(s):

Dendritic Cells ◽

Confocal Microscopy ◽

Fabry Disease ◽

Nerve Damage ◽

Corneal Confocal Microscopy ◽

Corneal Nerve

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Corneal Nerve Loss Detected With Corneal Confocal Microscopy Is Symmetrical and Related to the Severity of Diabetic Polyneuropathy

Diabetes Care ◽

10.2337/dc13-0193 ◽

2013 ◽

Vol 36 (11) ◽

pp. 3646-3651 ◽

Cited By ~ 74

Author(s):

I. N. Petropoulos ◽

U. Alam ◽

H. Fadavi ◽

O. Asghar ◽

P. Green ◽

...

Keyword(s):

Confocal Microscopy ◽

Diabetic Polyneuropathy ◽

Corneal Confocal Microscopy ◽

Corneal Nerve

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Corneal confocal microscopy detects improvement in corneal nerve morphology with an improvement in risk factors for diabetic neuropathy

Diabetic Medicine ◽

10.1111/j.1464-5491.2011.03372.x ◽

2011 ◽

Vol 28 (10) ◽

pp. 1261-1267 ◽

Cited By ~ 79

Author(s):

M. Tavakoli ◽

P. Kallinikos ◽

A. Iqbal ◽

A. Herbert ◽

H. Fadavi ◽

...

Keyword(s):

Risk Factors ◽

Confocal Microscopy ◽

Diabetic Neuropathy ◽

Corneal Confocal Microscopy ◽

Corneal Nerve ◽

Corneal Nerve Morphology

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Using corneal confocal microscopy to compare Mecobalamin intramuscular injections vs oral tablets in treating diabetic peripheral neuropathy: a RCT

Scientific Reports ◽

10.1038/s41598-021-94284-4 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Yuanjin Zhang ◽

Dongsheng Fan ◽

Yixuan Zhang ◽

Shuo Zhang ◽

Haikun Wang ◽

...

Keyword(s):

Peripheral Neuropathy ◽

Confocal Microscopy ◽

Nerve Fibre ◽

Diabetic Peripheral Neuropathy ◽

Controlled Study ◽

Oral Tablet ◽

Injection Treatment ◽

Intramuscular Injections ◽

Corneal Confocal Microscopy ◽

Corneal Nerve

AbstractThis randomized controlled study used corneal confocal microscopy (CCM) to compare the efficacy of Mecobalamin intramuscular injections vs oral tablets in treating mild to moderate diabetic peripheral neuropathy (DPN) by detecting early nerve fiber repair. Enrolled patients were randomized approximately 1:1 to receive Mecobalamin intramuscular injections (0.5 mg/day, 3 times/week) or Mecobalamin oral tablets (1.5 mg/day) for 8 weeks. Primary outcome was change of inferior whorl length (IWL) from baseline. Secondary outcomes included changes of corneal nerve fibre length (CNFL), corneal nerve fibre density (CNFD), corneal nerve branch density (CNBD) and the Survey of Autonomic Symptoms (SAS). 15 (93.75%) patients in the injection group and 17 (89.47%) patients in the tablet group completed the study. The injection treatment significantly improved patients’ IWL from baseline (21.64 ± 3.00 mm/mm2 vs 17.64 ± 4.83 mm/mm2, P < 0.01) while the tablet treatment didn’t. Additionally, the injection treatment led to significantly improved CNFL, CNBD and SAS from baseline (all P < 0.05) while the tablet treatment did not. No patient experienced any adverse events. In conclusion, CCM is sensitive enough to detect the superior efficacy of 8-week Mecobalamin intramuscular injection treatment for DPN compared to the oral tablet treatment.ClinicalTrials.gov registration number: NCT04372316 (30/04/2020).

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Combining In Vivo Corneal Confocal Microscopy with Deep Learning-based Analysis Reveals Sensory Nerve Fiber Loss in Acute SIV Infection

10.1101/2020.04.19.048926 ◽

2020 ◽

Author(s):

Megan E. McCarron ◽

Rachel L. Weinberg ◽

Jessica M. Izzi ◽

Suzanne E. Queen ◽

Stuti L. Misra ◽

...

Keyword(s):

Fractal Dimension ◽

Deep Learning ◽

Confocal Microscopy ◽

Nerve Fiber ◽

Fiber Length ◽

Sensory Nerve ◽

Corneal Confocal Microscopy ◽

Siv Infection ◽

Corneal Nerve

AbstractPurposeTo characterize corneal subbasal nerve plexus morphologic features using in vivo corneal confocal microscopy (IVCM) in normal and SIV-infected macaques and to implement automated assessments using novel deep learning-based methods customized for macaque studies.MethodsIn vivo corneal confocal microscopy images were collected from both male and female age-matched specific-pathogen free rhesus and pigtailed macaques housed at the Johns Hopkins University breeding colony using the Heidelberg HRTIII with Rostock Corneal Module. We also obtained repeat IVCM images of 12 SIV-infected animals including pre-infection and 10 day post-SIV infection time-points. All IVCM images were analyzed using a novel deep convolutional neural network architecture developed specifically for macaque studies.ResultsDeep learning-based segmentation of subbasal nerves in IVCM images from macaques demonstrated that corneal nerve fiber length (CNFL) and fractal dimension measurements did not differ between species, but pigtailed macaques had significantly higher baseline corneal nerve fiber tortuosity than rhesus macaques (P = 0.005). Neither sex nor age of macaques was associated with differences in any of the assessed corneal subbasal nerve parameters. In the SIV/macaque model of HIV, acute SIV infection induced significant decreases in both corneal nerve fiber length and fractal dimension (P= 0.01 and P= 0.008 respectively).ConclusionsThe combination of IVCM and objective, robust, and rapid deep-learning analysis serves as a powerful noninvasive research and clinical tool to track sensory nerve damage, enabling early detection of neuropathy. Adapting the deep-learning analyses to human corneal nerve assessments will refine our ability to predict and monitor damage to small sensory nerve fibers in a number of clinical settings including HIV, multiple sclerosis, Parkinson’s disease, diabetes, and chemotherapeutic neurotoxicity.

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Evaluation of Corneal Nerves and Dendritic Cells By in Vivo Confocal Microscopy After Descemet’s Membrane Keratoplasty For Bullous Keratopathy

10.21203/rs.3.rs-1197425/v1 ◽

2022 ◽

Author(s):

Takahiko Hayashi ◽

Atsuyuki Ishida ◽

Akira Kobayashi ◽

Takefumi Yamaguchi ◽

Nobuhisa Mizuki ◽

...

Keyword(s):

Dendritic Cells ◽

Confocal Microscopy ◽

Bullous Keratopathy ◽

Dependent Manner ◽

In Vivo Confocal Microscopy ◽

Descemet Membrane Endothelial Keratoplasty ◽

Corneal Nerves ◽

Corneal Nerve ◽

Number Of Branches

Abstract This study evaluated changes in corneal nerves and the number of dendritic cells (DCs) in corneal basal epithelium following Descemet membrane endothelial keratoplasty (DMEK) surgery for bullous keratopathy (BK). Twenty-three eyes from 16 consecutive patients that underwent DMEK for BK were included. Eyes of age-matched patients that underwent pre-cataract surgery (12 eyes) were used as controls. In vivo confocal microscopy was performed pre- and postoperatively at 6, 12, and 24 months. Corneal nerve length, corneal nerve trunks, number of branches, and the number of DCs were determined. The total corneal nerve length of 1634.7 ± 1389.1 μm /mm2 before surgery was significantly increased in a time-dependent manner to 4485.8 ± 1403.7 μm /mm2, 6949.5 ± 1477.1 μm /mm2, and 9389.2 ± 2302.2 μm /mm2 at 6, 12, and 24 months after DMEK surgery, respectively. The DC density in BK cornea pre- and postoperatively at 6 months was significantly higher than in the controls, and decreased postoperatively at 12 and 24 months and was significantly lower than that at 6 months postoperatively. Thus, our results suggest that DMEK can repair and normalize the corneal environment.

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